Base- and Sugar-Modified Cytidine MonophosphateN-Acetylneuraminic Acid (CMP-Neu5Ac) Analogues - Synthesis and Studies with α(2-6)-Sialyltransferase from Rat Liver

Abstract

The reaction of sialyl phosphites 1, 22a‐d, 28, 39, and 45 with acyl‐protected riboside 5‐phosphorous acids 2a,b and 23 directly furnished, without addition of a catalyst, under phosphite/phosphate exchange the corresponding β‐configured sialyl riboside monophosphates 3a,b, 24a‐d, 29, 46, and 47. The synthesis of the starting materials, formation of the products, and their treatment with sodium methanolate in methanol and subsequent hydrolysis of the sialic acid ester moiety to provide the unprotected target molecules 4a,b, 25a‐d, 30, 48, and 49 is described. Investigations with α(2‐6)‐sialyltransferase from rat liver showed that base replacement in CMP‐Neu5Ac (4a,b) is not tolerated by the enzyme but that modifications of the 5‐, 8‐, or 9‐position of the neuraminic acid residue (25a‐d, 30, 48, 49) are tolerated.

Pasteurella multocida sialic acid aldolase: a promising biocatalyst

“…This compound is important for understanding the significance of 8-OMe modification of Neu5Ac in nature and the biological functions of sialosides containing Neu5Ac8OMe. The applicability of PmNanA in the efficient synthesis of Neu5Ac8OMe is very significant since the chemical synthesis of this compound is tedious and low yielding (Dufner et al 2000;Khorlin and Privalova 1970), and previous aldolase-catalyzed enzymatic synthesis was either not successful (Augé et al 1988) or only produced trace amount of product (Augé et al 1990). Also as demonstrated in this study, a much larger amount of the enzyme and a longer incubation time will be required to produce a similar amount of the Neu5Ac8OMe product using EcNanA.…”

Glycosyltransferase Inhibitors

“…23.17). Inhibitors should consist of the CMP moiety, which was found to be essential [193], a a-hydroxyphosphonate moiety, and a planar aromatic ring system, which should mimic the planar glycosyl carbonium ion transition state of the neuraminic acid. The distance between the two negative charges is five bonds -the same as assumed for the natural situation (Fig.…”

Chemoenzymatic synthesis of C8-modified sialic acids and related α2–3- and α2–6-linked sialosides

“…16–18 These methods, however, are inefficient, lengthy, and tedious. In comparison, enzyme-catalyzed reactions often offer great advantages and are considered attractive and practical approaches for the synthesis of sialosides including those containing uncommon sialic acid forms.…”